DESCRIPTION: Light-chain-associated amyloidosis (AL amyloidosis) is a plasma-cell dyscrasia characterized by systemic fibrillar deposition of monoclonal light chains and related fragments; the resultant pathology leads to progressive organ dysfunction and eventual death. A corticosteroid dexamethasone (DEX)/alpha-interferon (IFN) regimen in patients with multiple myeloma has proven beneficial in an initial limited clinical trial. Based on these preliminary findings, a Southwest Oncology Group-wide Phase II study (SWOG S9628) has been initiated to determine the efficacy of this therapeutic regimen in a larger patient population. The protocol includes a research arm designed to investigate the relationship between specific properties of amyloidogenic light chains and the clinical manifestations of AL amyloidosis. The four specific aims of the proposed research are as follows: 1) To characterize serologically the phenotypic features of the amyloid precursor monoclonal immunoglobulin and to ascertain the relationship between this information and particular disease characteristics; 2) to determine the serum and/or urinary concentrations of amyloidogenic precursor Igs as a measure of the response to induction and maintenance therapy and to analyze the prognostic relevance of these data; 3) to identify and characterize the monoclonal bone marrow plasma-cell population and to establish the diagnostic importance of this information; and 4) to determine the therapeutic and prognostic utility of a histologic staging system for AL amyloid deposition from fat aspirates. This exploratory grant application is designed to provide an essential research component to the SWOG S9628 protocol that will result in new knowledge on the pathogenesis of AL amyloidosis: The ultimate goal is to improve the prognosis of patients with this fatal disease.